COVID-19 and diabetes in children

Prosperi Sara,Chiarelli Francesco 대한소아내분비학회 2022 Annals of Pediatirc Endocrinology & Metabolism Vol.27 No.3

This review describes the impact of coronavirus disease 2019 (COVID-19) in children and adolescents, investigating changes in diabetes presentation during the COVID-19 pandemic, possible links between severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection and diabetes, and mechanisms of pancreatic β-cell destruction. Although glycemic control in individuals with already known diabetes mellitus did not worsen during the pandemic, there was a worrying increase in diabetic ketoacidosis in children with new-onset diabetes, probably due to containment measures and delayed access to emergency departments. Moreover, new evidence suggests that SARS-CoV-2 has the capacity to directly and indirectly induce pancreatic β-cell destruction, and the risk of newly diagnosed diabetes after COVID-19 increased in both children and adults. While long-term studies continue to follow children with SARS-CoV-2 infection, this review discusses available findings on the relationship between COVID-19 and diabetes. It is important to emphasize the need to maintain close links between families of children with chronic conditions and their pediatricians, as well as to promote early access to healthcare services, in order to reduce dangerous delays in diabetes diagnosis and prevent diabetic ketoacidosis.

Ciliopathies in pediatric enodcrinology

Cicolini Ilenia,Blasetti Annalisa,Chiarelli Francesco 대한소아내분비학회 2023 Apem Vol.28 No.1

Ciliopathies are a group of disorders that involve many organs and systems. In this review, we consider the role of the cilium in multiorgan pathology with a focus on endocrinological aspects. Identification of new genes and mutations is the major challenge in development of a tailored and appropriate therapy. It is expected that new mutations will be identified to characterize ciliopathies and promote new therapies.

Growth plate extracellular matrix defects and short stature in children

Saltarelli Maria Alessandra,Quarta Alessia,Chiarelli Francesco 대한소아내분비학회 2022 Apem Vol.27 No.4

Many etiological factors causing short stature have already been identified in humans. In the last few years, the advent of new techniques for the detection of chromosomal and molecular abnormalities has made it possible to better identify patients with genetic causes of growth failure. Some of these factors directly affect the development and growth of the skeleton, since they damage the epiphyseal growth plate, where linear growth occurs, influencing chondrogenesis. In particular, defects in genes involved in the organization and function of the growth plate are responsible for several well-known conditions with short stature. These genes play a pivotal role in various mechanisms involving the extracellular matrix, intracellular signaling, paracrine signaling, endocrine signaling, and epigenetic regulation. In this review, we will discuss the genes involved in extracellular matrix disorders. The identification of genetic defects in linear growth failure is important for clinicians and researchers in order to improve the care of children affected by growth disorders.

Deciphering short stature in children

Nella Polidori,Valeria Castorani,Angelika Mohn,Francesco Chiarelli 대한소아내분비학회 2020 Annals of Pediatirc Endocrinology & Metabolism Vol.25 No.2

Short stature is a common reason for referral to pediatric endocrinologists. Multiple factors, including genetic, prenatal, postnatal, and local environmental factors, can impair growth. The majority of children with short stature, which can be defined as a height less than 2 standard deviation score below the mean, are healthy. However, in some cases, they may have an underlying relevant disease; thus, the aim of clinical evaluation is to identify the subset of children with pathologic conditions, for example growth hormone deficiency or other hormonal abnormalities, Turner syndrome, inflammatory bowel disease, or celiac disease. Prompt identification and management of these children can prevent excessive short stature in adulthood. In addition, a thorough clinical assessment may allow evaluation of the severity of short stature and likely growth trajectory to identify the most effective interventions. Consequently, appropriate diagnosis of short stature should be performed as early as possible and personalized treatment should be started in a timely manner. An increase in knowledge and widespread availability of genetic and epigenetic testing in clinical practice in recent years has empowered the diagnostic process and appropriate treatment for short stature. Furthermore, novel treatment approaches that can be used both as diagnostic tools and as therapeutic agents have been developed. This article reviews the diagnostic approach to children with short stature, discusses the main causes of short stature in children, and reports current therapeutic approaches and possible future treatments.

p53 Codon 72 Genetic Polymorphism in Asthmatic Children: Evidence of Interaction With Acid Phosphatase Locus 1

Patrizia Saccucci,Alberto Verrotti,Cosimo Giannini,Marcello Verini,Francesco Chiarelli,Anna Neri,Andrea Magrini 대한천식알레르기학회 2014 Allergy, Asthma & Immunology Research Vol.6 No.3

Several lines of evidence are implicating an increased persistence of apoptotic cells in patients with asthma. This is largely due to a combination ofinhibition, or defects in the apoptotic process and/or impaired apoptotic cell removal mechanisms. Among apoptosis-inducing genes, an importantrole is played by p53. In the present study, we have investigated the possible relationship between p53 codon 72 polymorphism and asthma and theinteraction with ACP1, a genetic polymorphism involved in the susceptibility to allergic asthma. We studied 125 asthmatic children and 123 healthysubjects from the Caucasian population of Central Italy. p53 codon 72 and ACP1 polymorphisms were evaluated using a restriction fragment lengthpolymorphism-polymerase chain reaction (RFLP-PCR) method. There is a statistically significant association between p53 codon 72 polymorphismand allergic asthma: Arg/Arg genotype is more represented in asthmatic patients than in controls (P=0.018). This association, however, is presentin subjects with low ACP1 activity A/A and A/B only (P=0.023). The proportion of children with A/A and A/B genotype carrying Arg/Arg genotype issignificantly high in asthmatic children than in controls (OR=1.941, 95% C.I. 1.042-3.628). Our finding could have important clinical implications sincethe subjects with A/A and A/B genotypes of ACP1 carrying Arg/Arg genotype are more susceptible to allergic asthma than Pro/Pro genotype.

Insulin resistance and type 2 diabetes in children

Valeria Castorani,Nella Polidori,Cosimo Giannini,Annalisa Blasetti,Francesco Chiarelli 대한소아내분비학회 2020 Annals of Pediatirc Endocrinology & Metabolism Vol.25 No.4

Type 2 diabetes (T2D) is an emerging health risk in obese children and adolescents. Both environmental (lack of physical activity, excess nutritional intake, sedentary lifestyle) and genetic factors contribute to this global epidemic. The growing prevalence of T2D in youth is also associated with a consistently increased incidence of metabolic and cardiovascular complications. Insulin resistance (IR), i.e., whole-body decreased glucose uptake in response to physiological insulin levels, determines impaired glucose homeostasis and it is recognized as cardinal trigger of T2D and cardiovascular disease in both adults and children. In particular, IR and beta-cell dysfunction lead to the persistent hyperglycemia which characterizes T2D. Indeed, both pathological states influence each other and presumably play a crucial, synergistic role in the pathogenesis of T2D, although the precise mechanisms are not completely understood. However, beta-cell dysfunction and IR induce impaired glucose metabolism, thus leading to the progression to T2D. Therefore, understanding the mechanisms correlated with the decline of beta-cell function and IR is crucial in order to control, prevent, and treat T2D in youth. This review focuses on the current knowledge regarding IR and T2D in children and adolescents and showcases interesting opportunities and stimulating challenges for the development of new preventative approaches and therapeutic strategies for young patients with T2D.

Usefulness of nBos d 4, 5 and nBos d 8 Specific IgE Antibodies in Cow’s Milk Allergic Children

Anna Cingolani,Sabrina Di Pillo,Marzia Cerasa,Daniele Rapino,Nicola Pietro Consilvio,Marina Attanasi,Alessandra Scaparrotta,M. Loredana Marcovecchio,Angelika Mohn,Francesco Chiarelli 대한천식알레르기학회 2014 Allergy, Asthma & Immunology Research Vol.6 No.2

Purpose: The aim of study was to assess the value of recombinants in predicting the degree of symptoms in children with and without anaphylaxisto cow’s milk. Methods: The study included 79 children (70±40 months) referred to the Allergological Unit of the Pediatric Department betweenthe years 2008-2012. Group A was composed of 17 children (78±49.6 months) with anaphylaxis after ingestion of milk. Group B was composed of62 children (73.1±38.6 months) without a history of anaphylaxis, but with less severe symptoms (gastrointestinal and/or skin symptoms). All patientsfrom Group B had a positive open challenge with cow’s milk. All patients underwent an allergic evaluation and blood samples were collectedto test for IgE to recombinans of milk (nBos d 4, 5, 8). Results: A significant difference in nBos d 8 emerged with higher levels in Group A (median[IQR]=2.80 [0.91-16.1]) than B (0.65 [0.24-1.67]; P=0.006), whereas there were no statistically significant differences for nBos d 4 and 5. The recombinants’sum was higher in Group A than B: 8.39 [2.72-41.39] vs 3.04 [1.85-7.31] kUA/L; P=0.044. The recombinant nBos d 8 was superior to the otherrecombinants in identifying children at risk for anaphylaxis, with an area under the curve of 0.718 (95% CI, 0.57-0.86, P=0.006). Considering acutoff of 1.8 kUA/L, nBos d 8 had the most favorable sensitivity and specificity ratio (sensitivity=0.65, specificity=0.77) with an odd ratio of 6.02(95% C.I: 1.89-19.23). Conclusions: This study suggested 2 phenotypes of allergic children, “high-anaphylaxis-risk” and “milder-risk”. These typescan be differentiated through measuring the level of IgE to nBos d 8. Key Words: Child; symptoms; milk; allergy; recombinant proteins